Search

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

DRAGEN rapidly identifies diverse types of genetic variants.

Al-Hasani, Gowrishankar et al. show that long-range GABAergic projections from the ventral tegmental area to the ventral nucleus accumbens shell inhibit cholinergic activity to promote reward reinforcement.

Single-cell mapping of chromatin accessibility, DNA methylation and RNA expression during gastrulation in mouse embryos shows characteristic epigenetic changes that accompany formation of the primary germ layers.

The extent, origins and consequences of genetic variation within human cell lines are studied, providing a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research.

Whole-genome sequencing, transcriptome sequencing and single-cell analysis of primary and metastatic pancreatic adenocarcinoma identify molecular subtypes and intratumor heterogeneity.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

David Wong, Howard Chang and colleagues report the identification of long noncoding RNAs transcribed from the promoters of cell cycle genes. Many of these RNAs have periodic expression during the cell cycle and are regulated by oncogenic stimuli, stem cell differentiation or DNA damage.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

The tumour microenvironment (TME) may change in response to cancer treatments such as KRAS G12C inhibition, with potential implications for combination therapies. Here, the authors provide an antibody panel and workflow for analysing the TME with imaging mass cytometry in pre-clinical mouse models.

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. Here the authors perform single-cell omics analyses in CVID-discordant monozygotic twins and show epigenetic and transcriptional alterations associated with activation in memory B cells.

Analyses of both natural and experimental evolution suggest that adaptation depends on the evolutionary past and adaptive potential decreases over time. Here, by tracking yeast adaptation with DNA barcoding, the authors show that such evolutionary phenomena can be observed even after a single adaptive step.

'Silver-bullet' approaches to conservation assume that conservation strategy can be based on the distribution of species in one or two well known taxonomic groups, as there is high cross-taxon congruence in large-scale patterns of biodiversity. Although birds, mammals and amphibians show similar patterns in terms of overall species richness, the distribution of threatened and rare species is found to be different in each group.

Eukaryotic replisomes are multiprotein complexes. Here the authors reveal two distinct stressed replisomes, associated with DONSON and FANCM, displaying a bias in replication timing and chromatin domain.

Targeted CRISPR libraries expand the use of genetic screens across experimental conditions. Here, the authors develop a method for generating and analysing small scale custom CRISPR libraries and use it in the human and livestock pathogen Toxoplasma gondii to identify virulence factors in mice.

Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. Here the authors show that MLKL trafficking and plasma membrane accumulation are crucial necroptosis checkpoints, and that accumulation of phosphorylated MLKL at intercellular junctions promotes necroptosis.

Phylogenetic comparative methods applied to datasets of body size in five major vertebrate clades show that rates of speciation and morphological evolution are positively related at broad macroevolutionary scales but with heterogeneity in the strength and direction of these associations at finer scales.

A state-of-the-art generative artificial intelligence model of a video game is introduced to allow the support of human creative ideation, with the analysis of user study data highlighting three necessary capabilities, namely, consistency, diversity and persistency.

Whether and how highly penetrant NDD (neurodevelopmental disorder) genes such as Syngap1 regulate sensorimotor integration are not fully understood. This study shows that Syngap1 expression in cortical projection neurons promotes cognitive abilities in mice through forming distributed networks that integrate sensory information with motor signals, a dynamic process required for perception and attention.

Longitudinal deep lipidome profiling reveals >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation.

Genetic variation in mitochondrial DNA can influence human traits, but it is not as well studied in association with complex traits. Here, the authors find associations between mitochondrial haplogroups and genetic variation and neuroticism.

Sorting nexin 27 (SNX27) regulates endosomal sorting of glutamate receptors. Loo et al.show that SNX27 is localized to recycling endosomes within dendritic spines where it interacts with glutamate receptors, allowing them to be shuttled to the postsynaptic membrane.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Mutations in RAS oncogenes and related pathways are frequent in lung cancers. Here, the authors derive a RAS gene expression signature and a machine learning classifier to predict drug response and clinical outcomes in lung adenocarcinoma and other solid tumours, with improved performance over KRAS mutations alone.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

A machine learning approach for refinement of somatic variant calls automates this process and reduces bias stemming from inter-reviewer variability.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Treating malignant pleural mesothelioma (MpM) is challenging due to a lack of druggable genes, but other molecular features could be clinically useful. Here the authors profile mRNA translation dysregulation in MpM cell lines using polysome profiling, and identify mTORC1 and 2 as potential pharmacological targets.

Following global DNA demethylation, mouse gonadal primordial germ cells undergo remodelling of repressive chromatin modifications, resulting in a sex-specific signature that is required to safeguard the transcriptional program.

In mice, the neural mechanisms underlying aversive social learning, specifically avoidance and fear after defeat, involve oxytocin signalling in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part.

Parallel, genome-wide methylation and transcriptional profiling from a single cell (scM&T-seq) enables the discovery of associations between transcriptional and epigenetic variation.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Single-cell bisulfite sequencing (scBS-seq) allows robust DNA methylation analysis in rare cells and heterogeneous populations.

What factors explain variation in the pace and trajectory of evolutionary divergence between lineages? Here, the authors show that a proxy measure for sexual selection intensity predicts both the rate and direction of plumage colour evolution in a diverse radiation of New World passerine birds.

Respiratory infections occur throughout life but how this shapes the lung immune system through time is unclear. Wack and colleagues show that a previous influenza infection recruits monocytes to the lung, which then assume an alveolar macrophage-like phenotype and mediate long-term antibacterial protection.

Pancreatic ductal adenocarcinoma (PDAC) is a complex disease and its underlying epigenomic heterogeneity is not fully understood. Here, the authors utilize patient-derived PDAC xenografts to define the epigenomic landscape of PDAC, highlighting chromatin states linked to differing disease aggressiveness and survival.